Effects of gender, age, diabetes mellitus and renal and hepatic impairment on tadalafil pharmacokinetics

Abstract

AimsTo evaluate the effects of gender, age, diabetes mellitus, renal and hepatic impairment on tadalafil pharmacokinetics and tolerability. MethodsSix single-dose (5, 10 or 20 mg orally) clinical pharmacology studies were conducted in the UK, Belgium, Poland and Germany in healthy male and female subjects, elderly subjects and subjects with diabetes mellitus, renal impairment, end-stage renal failure (ESRF) or hepatic impairment. The gender study also incorporated administration of 10 mg tadalafil daily for 10 days. ResultsSystemic exposure in the elderly was 25% greater than in young subjects (mean AUC ratio 1.25; 90% confidence interval 0.972, 1.61). The AUC was 19% lower in subjects with diabetes mellitus than in healthy age/gender-matched controls. Pharmacokinetics in female subjects were essentially similar to those in males. Exposure in subjects with mild or moderate renal insufficiency was approximately twice that in healthy subjects. The mean AUC for the major metabolite (total methylcatechol glucuronide) in the presence of ESRF was three times the mean for healthy subjects. Haemodialysis contributed negligibly to elimination of tadalafil or the metabolite. Hepatic impairment had negligible effects on exposure. The most common adverse events in these six studies were headache, back pain and myalgia. A 10-mg dose was not well tolerated by subjects with moderate renal dysfunction in this study. ConclusionsNo clinically significant effect of gender, age, diabetes mellitus or hepatic impairment on tadalafil pharmacokinetics was observed. Renal insufficiency resulted in increased systemic exposure. Tadalafil was not associated with any serious clinically significant adverse events or study discontinuations due to adverse events.

Positive effect of tadalafil, a phosphodiesterase-5 inhibitor, on fracture healing in rat femur

“…Tadalafil has a longer half-life than sildenafil (17.5 hours versus 4 hours), which permits single daily dosing, and, unlike sildenafil, tadalafil absorption is unaffected by food or alcohol consumption. [14,33] Tadalafil metabolism in the geriatric population and in patients with mild to moderate hepatic impairment is similar to that in the general population, [34,35] whereas the metabolism of sildenafil is altered in these subgroups. [36] Finally, the PDE5 selectivity of tadalafil is higher than that of sildenafil, which results in a better adverse effect profile.…”

Plasma Concentrations of Tadalafil in Children With Pulmonary Arterial Hypertension

“…The t max value of tadalafil in hyperlipidemic rats tended to be extended as compared with that in control rats, but the difference was not significant. 23 Therefore, together with the fact that tadalafil is a drug with a low hepatic extraction ratio, 8,12 its disposition seems rather susceptible to changes in intrinsic metabolic clearance (CL int ) and/or the UBF (f u ) of the drug.…”

“…In addition, it was reported that gender, age, and hepatic impairment have no effect on the pharmacokinetics of tadalafil in adults, although systemic exposure in the elderly was 25% greater than in young subjects. 12 Although tadalafil had negligible renal clearance, total clearance of tadalafil was reduced by mild or moderate renal insufficiency, with a corresponding prolongation of t 1/2 and exposure approximately twice that in healthy subjects. 12 The mechanisms underlying the decrease of total clearance associated with renal impairment remain unclear.…”

“…12 Although tadalafil had negligible renal clearance, total clearance of tadalafil was reduced by mild or moderate renal insufficiency, with a corresponding prolongation of t 1/2 and exposure approximately twice that in healthy subjects. 12 The mechanisms underlying the decrease of total clearance associated with renal impairment remain unclear. These results indicate that careful monitoring of tadalafil may be required in the treatment of children with immature or decreased renal function.…”

The efficacy of udenafil in end-stage renal disease patients undergoing hemodialysis

“…14 Similarly, the results of the use of tadalafil in an HD patient group showed that it is effective and welltolerated. 40 In our study of an HD patient group, udenafil was found to be an effective treatment for ED and other accompanying sexual function disorders. All 31 patients included in our study provided positive feedback regarding their ongoing treatment at the checkup after 1 month, which is another positive result.…”